Association of Tacrolimus Intrapatient Variability and One-Year Outcome in Kidney Transplant Patients of National Kidney and Transplant Institute, January 2016-December 2020: A Retrospective Study

Background: Tacrolimus provides an effective means of preventing allograft rejection. However, it has been presented to be challenging due to its narrow therapeutic window and pharmacokinetic variability, both interpatient and intra-patient. Thus, intra-patient variability (IPV) of tacrolimus trough concentrations has been closely monitored as it has become a prognostic marker for predicting transplant outcomes. Methods: A retrospective analysis of 1,240 kidney transplant patients and was under Tacrolimus during the study duration were included. Clinico-demographic and kidney transplant profile including Tacrolimus Intra-patient variability (Tac IPV) value were utilized for evaluation. Tac IPV was calculated using the coefficient of variability (CV), while mean concentrations were derived from all Tac concentrations between 6 and 12months. The group was divided into low and high IPV based on the median value of CV in the cohort. Statistical analyses were conducted using fisher exact test to determine the association between the Tac IPV and outcome of post-transplant cases over one year. Results: Based on the median coefficient of variation (13.4%), patients were evenly divided into low and high IPV groups (n = 620 each). High IPV was observed from younger patients, while no significant differences were noted in other baseline characteristics of the patients. High Tac IPV was associated with higher serum creatinine levels at both 6- and 12- month post-transplant. The incidence of doubling serum creatinine – a marker for declining renal function – was significantly higher in the high IPV group at both 6 months (15.81% vs. 9.68%) and 12 months (14.52% vs. 7.74%) while no significant differences were observed between the IPV groups in biopsy-proven acute rejection, proteinuria, graft survival, or patient survival. Conclusion: High IPV was not significantly associated with acute rejection, proteinuria and one-year graft and patient survival but was correlated with increased risk of renal function deterioration. The findings underscore the significance of maintaining stable Tacrolimus exposure. Monitoring and minimizing Tacrolimus IPV may serve as a modifiable factor to improve kidney transplant outcomes.